DE102017127017A1 - A disposable automated filtration apparatus and method for controlling an automated disposable filtration apparatus - Google Patents

Abstract

An automated one-way filtration device (10), particularly for large volume filtration processes, includes a non-filtrate inlet (56), one or more filter elements, a filtrate exit (58), and sensors for sensing particular process parameters and control devices to adjust particular process parameters. The sensors and control devices are connected to an external control and control system (78), which is set up for the evaluation and processing of sensor data and for controlling the control devices based on one or more control algorithms.

Description

The invention relates to an automated disposable filtration device, which is particularly suitable for large-volume filtration processes. The invention further relates to a method for controlling such an automated disposable filtration device.

In the area of single-use technology development for biopharmaceutical applications, filtration elements are becoming increasingly popular and are now widely used. For example, in recent years, disposable filtration technologies have evolved steadily and are no longer used only in the laboratory and process development fields. Rather, disposable filtration elements are now also used in commercial manufacturing processes of pharmaceutical products for the clinical phases 1 to 3 (Developmental stages in drug development) or in the commercial production of such drugs in use. Disposable filtration devices currently available on the market are limited to smaller filter elements, which in turn are limited only to the pure functionality of "filtering".

The WO 2017/032560 A1 shows a fully pre-sterilizable, ready-to-use and integrity-testable disposable filtration device designed for large volume filtration processes. This disposable filtration device comprises a plurality of standard size disposable filter capsules arranged in a predetermined pattern and interconnected by conduits. The filter capsules are supported by a rigid bracket.

In the case of the previous disposable filtration elements, however, the question of integration into automated processes has not been considered. With the introduction of disposable filtration technology into commercial production described above, in addition to the pure scaling, ie the required filter size and thus filtration area, the need for automated filtration processes is also increasing. This requires the embedding of filtration elements in hose lines, plastic piping, disposable sensors and connection systems, which can then become an integrated process solution by connecting to a suitable control and control system.

Thus, in the field of disposable filtration technology, there is a need for a disposable, disposable filtration device that enables a partially or fully automated filtration process, particularly on a large scale. The object of the invention is to meet this need.

This object is achieved by an automated disposable filtration device having the features of claim 1 and by a method for controlling an automated disposable filtration device having the features of claim 12. Advantageous and expedient embodiments of the device according to the invention and the method according to the invention are in the appended subclaims specified.

The automated disposable filtration device according to the invention is particularly intended for large-volume filtration processes and comprises a non-filtrate input, one or more filter elements (in one or more filter units), a filtrate output and sensors for detecting certain process parameters and control devices for setting certain process parameters. The sensors and control devices are connected to an external control and control system, which is set up for the evaluation and processing of sensor data and for controlling the control devices based on one or more control algorithms.

The invention is based inter alia on the recognition that an automation of a filtration process using disposable components - in comparison to conventional reusable systems with stainless steel components - due to the significantly higher, material-related risks, of greater importance. This is why process reliability in disposable systems is even more important. Through automation, manual operator errors or adjustments can be reduced or even completely eliminated. If errors still occur or start, this can be detected early. In addition, the constant determination, control, monitoring and adjustment of optimal process parameters can achieve a significant increase in efficiency. With the proposed disposable filtration device, it is possible to perform a complete filtration process with all or at least some process steps using the control and control system partially or fully automatically. Prerequisite for this are the sensors and control devices connected to the control and control system for the detection, control and possibly regulation of certain process-relevant parameters.

The sensors or control devices connected to the control and control system preferably comprise one or more of the following components, which are further preferably all designed as disposable components: a flow sensor arranged at the unfiltrate inlet; an input pressure sensor located at the unfiltrate inlet; a arranged at Unfiltrateingang Input control valve; a source liquid detector disposed at the filtrate exit; an exit control valve located at the filtrate exit; and an output pressure sensor located at the filtrate exit.

The inventive automated disposable filtration device preferably has a sterile air filter which is connected to a vent outlet of the disposable filtration device. The sensors or control devices then preferably also comprise a vent control valve inserted between the vent outlet and the sterile air filter and / or a venting liquid detector inserted between the vent outlet and the sterile air filter, wherein these in turn are further preferably designed as disposable components.

Preferably, the control devices further comprise an input-side feed pump whose delivery rate is adjustable. Further preferably, the delivery rate (automated) is adjustable.

• - Befüllen der Einweg-Filtrationsvorrichtung mit einem Benetzungsmedium und vollständige Entlüftung über den Sterilluftfilter;
• - Spülen und Benetzen der Einweg-Filtrationsvorrichtung oder des Filterelements;
• - Entleeren und Belüften der Einweg-Filtrationsvorrichtung durch statisches Leerlaufenlassen oder aktiv durch Leerdrücken mit Hilfe eines gasförmigen Mediums;
• - Pre-Use-Filter-Integritätstest mit einem gasförmigen Medium;
• - Befüllen der Einweg-Filtrationsvorrichtung mit einem flüssigen Produkt und vollständige Entlüftung;
• - Filtration eines flüssigen Produkts unter permanenter Überwachung des Eingangsdrucks bzw. Ausgangsdrucks und vorzugsweise der Durchflussrate;
• - Filtration eines flüssigen Produkts unter zwischenzeitlicher Nachentlüftung der Einweg-Filtrationsvorrichtung bei Bedarf;
• - Ausschieben von Produktrestflüssigkeit nach Beendigung der Filtration und Spülen mit Puffer oder Wasser oder einem anderen flüssigen Medium;
• - Entleeren und Belüften der Einweg-Filtrationsvorrichtung durch statisches Leerlaufenlassen oder aktiv durch Leerdrücken mit Hilfe eines gasförmigen Mediums; und
• - Post-Use-Filter-Integritätstest mit einem gasförmigen Medium.

The invention also provides a method for controlling an automated disposable filtration device according to the invention, wherein the control and control system performs at least partially automatically at least one of the following process steps:

• - filling the disposable filtration device with a wetting medium and complete venting via the sterile air filter;
• Rinsing and wetting the disposable filtration device or filter element;
• Emptying and aerating the disposable filtration device by static idling or actively by blanking with the aid of a gaseous medium;
• - Pre-use filter integrity test with a gaseous medium;
• - filling the disposable filtration device with a liquid product and complete deaeration;
• - Filtration of a liquid product with continuous monitoring of the inlet pressure and, preferably, the flow rate;
• - Filtration of a liquid product with intermediate post-venting of the disposable filtration device as needed;
• - expelling product residual fluid after completion of the filtration and rinsing with buffer or water or other liquid medium;
• Emptying and aerating the disposable filtration device by static idling or actively by blanking with the aid of a gaseous medium; and
• - Post-use filter integrity test with a gaseous medium.

Preferably, the process steps in the context of an overall process in the order mentioned are performed one after the other.

Certain preferred control and regulating operations are specified below, which can be carried out fully or partially automatically during one or more of the abovementioned process steps as part of a filtration process by means of the control and control system and the sensors or control devices connected thereto.

The filling of the disposable filtration device with wetting medium and / or product is carried out with continuous monitoring of the pressure at the inlet pressure sensor by the control and control system. The control and control system regulates the performance of the feed pump so that a predetermined maximum pressure is not exceeded.

When bleeding and / or venting the disposable filtration device via the sterile air filter, the bleed control valve is opened by the control and control system until the bleed liquid detector detects liquid. The control and control system then immediately closes the vent control valve.

When flushing and wetting the disposable filtration device or filter element, the control and control system obtains information from the flow sensor at the non-filtrate inlet and, based thereon, regulates the performance of the feed pump. At the same time, the control and monitoring system continuously monitors the pressure at the inlet pressure sensor. By means of the inlet control valve and / or the outlet control valve, the control and control system automatically adjusts and regulates a desired flushing capacity and desired pressure conditions.

When flushing and wetting the disposable filtration device or filter element, the control and control system alternately controls and / or cycles the vent control valve and output control valve so that controlled mixing and / or displacement of a fluid by another fluid occurs.

When emptying and venting the disposable filtration device by static idling or active by blanking with the aid of air The control and control system opens the bleed control valve and / or the output control valve to allow the liquid to drain.

When emptying and venting the disposable filtration device by static idling or actively by blanking with the aid of air, the control and control system signals based on information from the source liquid detector that the purge process is complete.

In the gaseous media pre-use filter integrity test, the control and control system drives an external integrity tester which performs the integrity test itself. The control and control system controls via a closing body (drive) to the control valves so that while the input control valve is closed and the output control valve and the vent control valve are open.

In the filtration of a product and / or expulsion of product residual fluid after completion of the filtration and rinsing with buffer or water and / or draining and aerating the disposable filtration device, the control and control system continuously monitors the pressure at the inlet pressure sensor. Alternatively or additionally, the control and control system obtains information from the flow sensor at the non-filtrate inlet. Based on this, the control and control system regulates the feed pump so that a certain filtration performance is achieved and / or that a predetermined pressure is not exceeded.

In the event of an excessive pressure increase, the control and control system throttles or shuts off the feed pump and / or closes the input control valve.

Upon expulsion of product residual fluid upon completion of filtration, the control and control system will signal based on information from the source fluid detector that the shedding process is complete.

• - 1 eine perspektivische Ansicht einer Einweg-Filtrationsvorrichtung mit Anschlussleitungen und weiteren Anschlusselementen; und
• - 2 eine schematische Seitenansicht einer erfindungsgemäßen automatisierten Einweg-Filtrationsvorrichtung.

Further features and advantages of the invention will become apparent from the following description and from the accompanying drawings, to which reference is made. In the drawings show:

• - 1 a perspective view of a disposable filtration device with connecting lines and other connection elements; and
• - 2 a schematic side view of an automated disposable filtration device according to the invention.

In 1 is a disposable filtration device 10 represented, which from the WO 2017/032560 A1 similar device is known. A plurality of filter capsules 12 comes from a rigid bracket 14 held in position in a predetermined arrangement (grid). The term "filter capsule" is to be understood here in general and is intended to designate any independently mountable assembly with one or more filter elements (membranes) which are installed in one or more filter units. The holder 14 includes support columns 16 passing through cross struts 18 connected to each other. stands 20 ensure a secure hold of the device 10 , At the cross struts 18 are holding means 22 for the individual filter capsules 12 intended. The filter capsules 12 are completely or at least largely due to rigid, pressure-stable pipelines 24 connected with each other. The concrete course of the pipelines exemplified here 24 is determined by the intended operation of the filtration device (parallel or series connection of the filter capsules 12 ), with the piping 24 the necessary branches 26 to the individual filter capsules 12 respectively. If necessary, the piping 24 on the bracket 14 attached. The essential components of the rigid holder 14 , the rigid housing of the filter capsules 12 and the rigid pipes 24 are all preferably made of the same material. This material and possibly other materials used in the device 10 Can be sterilized, in particular by means of gamma radiation, and autoclavable (for example for flexible hoses). The disposable filtration device 10 can thus be sterilized in the preassembled, ie ready for connection state and then packaged or packaged and then sterilized. The disposable filtration device 10 is designed for a large-volume filtration process. In particular, the filter capsules provide 12 Overall, a sufficiently large filtration area for such a process available.

In 1 Exemplary conduits, branches and connections are shown which are suitable for the integration of certain sensors and control devices for the automation of the disposable filtration device 10 can be provided. To a non-filtrate inlet of the rigid disposable filtration device 10 is via a piece of hose an inlet valve 28 connected. Upstream of the inlet valve 28 is a branch 30 provided, at whose one line branch a Tri-Clamp-Verbinndung 32 and at the other line branch a reinforced intermediate hose piece 34 and an input hose line connected thereto 36 with a first sterile connector 38 are provided. A filtrate output of the rigid disposable filtration device 10 is an outlet valve via a piece of hose 40 connected. Downstream of the exhaust valve 40 is a branch 42 provided, at whose one line branch a Tri-Clamp-Verbinndung 44 and at the other line branch a reinforced intermediate hose piece 46 and an outlet tubing connected thereto 48 with a second sterile connector 50 are provided. From a vent outlet of the disposable filtration device 10 carries a reinforced breather hose line 52 to an air filter holder containing a sterile air filter 54 wearing.

On the basis of in 2 shown exemplary configuration of a disposable filtration device 10 The integration of sensors and control equipment to automate the disposable filtration device 10 explained in more detail. For the sake of clarity, not all components and line branches are shown. As already mentioned are at a Unfiltrateingang 56 at a filtrate outlet 58 and at a vent outlet (or air inlet) 60 the disposable filtration device 10 each (possibly additional) hose connections for the sensors and control devices described below, all of which are designed as disposable components.

At the unfiltered entrance 56 are a flow sensor 62 for determining the volume flowing through per unit of time, an inlet pressure sensor 64 and an input control valve 66 intended. At the filtrate outlet 58 are a source liquid detector 68 , an output control valve 70 and an output pressure sensor 72 intended. At the vent outlet 60 are a vent control valve 74 and a venting liquid detector 76 intended.

Prerequisite for a complete or partial (single process steps) automation of the disposable filtration device 10 is basically that the integrated sensors and control devices via electrical lines with a control and control system 78 be connected and thus allow control of the overall process or the respective process step. The electrical lines are used on the one hand to operate the sensors and control devices and on the other hand, as far as provided for transmitting and / or receiving data or signals that are needed for the control and / or control. The data or signal transmission can alternatively also be done via radio. The control and control system 78 is not a disposable component, but one away from the filter capsules 12 arranged electronics containing suitable software and hardware for the evaluation and processing of sensor data and for controlling the control devices based on one or more control algorithms.

1. 1) Befüllen der Einweg-Filtrationsvorrichtung 10 mit einem Benetzungsmedium (z. B. Wasser) und vollständige Entlüftung über den Sterilluftfilter 54;
2. 2) Spülen und Benetzen der gesamten Einweg-Filtrationsvorrichtung 10 bzw. des Filterelements (filtrationswirksame Schicht);
3. 3) Entleeren und Belüften der Einweg-Filtrationsvorrichtung 10 durch statisches Leerlaufenlassen oder aktiv durch Leerdrücken mit Hilfe von Luft;
4. 4) Pre-Use-Filter-Integritätstest mit einem gasförmigen Medium, z. B. Luft;
5. 5) Befüllen der Einweg-Filtrationsvorrichtung 10 mit Produkt und vollständige Entlüftung (Prozess wie Schritt 1);
6. 6) Filtration des Produktes unter permanenter Überwachung und ggf. Kontrolle des Eingangsdrucks bzw. Ausgangsdrucks;
7. 7) Filtration des Produkts unter zwischenzeitlicher Nachentlüftung bei Bedarf;
8. 8) Ausschieben von Produktrestflüssigkeit nach Beendigung der Filtration zur Reduzierung von Verlusten und Spülen mit Puffer oder Wasser;
9. 9) Entleeren und Belüften der Einweg-Filtrationsvorrichtung 10 durch statisches Leerlaufenlassen oder aktiv durch Leerdrücken mit Luft (wie Schritt 3); und
10. 10) Post-Use-Filter-Integritätstest mit einem gasförmigen Medium, z. B. Luft (Prozess wie Schritt 4).

The following is an example with the disposable filtration device 10 feasible filtration process, which is divided into the following fully or partially automated individual steps:

1. 1) Fill the disposable filtration device 10 with a wetting medium (eg water) and complete deaeration via the sterile air filter 54 ;
2. 2) Rinse and wet the entire disposable filtration device 10 or the filter element (filtration-effective layer);
3. 3) Draining and aerating the disposable filtration device 10 by static idling or active by blanking with the aid of air;
4. 4) Pre-Use Filter Integrity Test with a gaseous medium, e.g. Air;
5. 5) Fill the disposable filtration device 10 with product and complete deaeration (process as step 1 );
6. 6) Filtration of the product under permanent monitoring and if necessary control of the inlet pressure or outlet pressure;
7. 7) Filtration of the product with intermediate post-deaeration if required;
8. 8) expelling product residual fluid after completion of filtration to reduce losses and rinse with buffer or water;
9. 9) Draining and aerating the disposable filtration device 10 by static idling or active by blanking with air (as in step 3 ); and
10. 10) post-use filter integrity test with a gaseous medium, e.g. B. Air (process as step 4 ).

To step 1 : When filling the disposable filtration device 10 with a wetting medium (eg water) using a feed pump 80 and the complete venting via the sterile air filter 54 There are several possibilities for errors, which entail particularly high risks due to the disposable technology.

A first risk is that the filling speed may be too high, so the air in the system does not have enough time to escape from the cavities and rise to the top. In this case, it may occur in the later filtration process to air releases, which then accumulate as air bubbles in the upper part of the system and thus adversely affect the filtration area and thus the filter efficiency.

The automatic control of this process step provides that filling the disposable filtration device 10 while continuously measuring and controlling the pressure at the inlet pressure sensor 64 he follows. The control and control system 78 in particular ensures that the feed pump 80 initially starts slowly to ensure a moderate filling process while not exceeding the maximum allowable pressure.

A second risk occurs especially at the end of the filling process when the operator of the disposable filtration device 10 the moment in which the wetting medium reaches the upper level and into the vent hose line 52 penetrates, does not recognize or too late, so that the wetting medium in the sterile air filter 54 penetrates. In this case, there is a risk that the sterile air filter 54 is wetted and thus has no or only a limited air permeability and thus its actual function of determination, namely to allow the air to escape from the system sterile, no longer or only partially meet.

By using the vent control valve 74 followed by the venting liquid detector 76 at the outlet of the breather hose line 52 , between the filter capsules 12 and the sterile air filter 54 , can with the help of the control and control system 78 first a controlled and slow venting by opening the venting valve slightly 74 respectively. Once the liquid level reaches the top of the disposable filtration device 10 reached and the liquid in the ascending vent hose line 52 penetrates, detects the venting liquid detector 76 this, and the control and management system 78 Immediately transmits a signal to the bleed control valve 74 , which is closed immediately, even before the liquid the sterile air filter 54 reached.

A third risk is that with manual squeeze valves, it may well happen that the operator has the feed pump 80 activated, at this time a manually operable valve at the pump outlet but not or not fully opened, or the input hose line 36 kinked in one place, which would very quickly create an overpressure in the hose system, which could bring the hose system or a hose connection to burst or cause a leak. Such a risk is particularly due to the background of the limited and often inconsistent pressure resistance of plastic tubing sets and transfer or bag systems. Leaving aside the risk of microbiological contamination, depending on the product and process step, leakage can also pose a significant health and economic risk.

Thanks to the automatically controlled filling process, by means of the control and control system 78 the speed of the feed pump 80 and thus controlling the flow rate. The inlet pressure sensor 64 can thereby the maximum allowable pressure of the disposable filtration device 10 monitor or, if necessary, adjust the pump capacity or the feed pump 80 stop completely, if z. B. a hose is blocked and therefore the maximum allowable pressure is reached.

To step 2 Also when rinsing and wetting the entire disposable filtration device 10 or the filter element (filtration-effective layer) can be made with manual operation errors that can be reasonably safely avoided without appropriate sensors only with the help of other tools. The rinsing process serves to wash out unwanted components and to condition and thus prepare the filter elements in the filter capsules 12 on the following filtration process. On the one hand, the amount of flushing medium, on the other hand, but also the flow rate of importance.

A first risk in this process step is that the flush volume in combination with the flushing performance or the recommended pressure conditions are not met and thus the filter unit is not optimally rinsed and prepared. Often the manufacturers give the filter capsules 12 what these process conditions should look like. For example, in this process step in addition to the flow and a certain pressure difference between input and output pressure may be helpful or even necessary.

With the help of the control and control system 78 , the information from the flow sensor 62 at the unfiltrate entrance 56 the disposable filtration device 10 can refer to the speed of the feed pump 80 the liquid flow are controlled. In parallel, with continuous measurement of the desired pressure conditions with the input control valve 66 a desired flushing power can be set and regulated.

A second risk in this process step is due to the fact that in the transition from wetting the filter to the filtration due to the fluid dynamics within the disposable filtration device 10 due to structural conditions, the rinsing and displacement of one medium (eg rinse water) with another medium (eg product) can take a relatively long time and can cause significant mixing phases. This can lead to a high consumption of rinse solution on the one hand, on the other hand, the loss of product can be very large, creating an economic risk represents. In manual mode, the user can use a disposable filtration device 10 do not control and reproducibly produce the conditions necessary to avoid this risk.

Thanks to the control and control system 78 can a precisely predefined, z. B. alternating clocking of the vent control valve 74 and the output control valve 70 be set to achieve and ensure optimal mixing or displacement of a liquid by another liquid under controlled conditions.

To step 3 : Draining and aerating the disposable filtration device 10 by static idling or active by air blanking requires full opening of the bleed control valve 74 and / or the inlet control valve 66 To ensure that air enters the disposable filtration device 10 can penetrate and the liquid due to gravity at the bottom filtrate outlet 58 can expire.

In manually performing this process step, the operator will not be able to determine if static emptying is adequate, as it will maintain the fluid level within the disposable filtration device 10 can not visually check. Unless the above-arranged control valves 74 and 66 may not or not be opened sufficiently, the liquid may not or not completely run off, and the disposable filtration device 10 does not empty completely.

For the automatic control of this process step, the output liquid detector 68 at the filtrate outlet 58 the disposable filtration device 10 included. The output liquid detector 68 sends a signal to the control and control system 78 , which signals to the operator that the draining process is completed and also in the lower part of the disposable filtration device 10 there is no residual liquid, although this may not be visually visible.

To step 4 : Before the intended filtration process, the filter elements are usually subjected to an integrity test with a gaseous medium, in particular air. The integrity test takes place z. B. with complete closure of the input control valve 66 via the vent outlet or air inlet 60 , At this time, the input side of the disposable filtration device becomes 10 with a defined test pressure, which is generated by an externally connected integration tester, applied to then check whether or how long this test pressure can be maintained. This period of time allows a conclusion on the integrity of the filter membranes.

When performing this process step manually, there is a risk that the operator of the disposable filtration device 10 the inlet control valve 66 not or has not closed sufficiently firmly, so that during the test phase small amounts of air can escape and affect the test result. This would lead to a false test result, so that the integrity test and possibly also the entire rinsing step would have to be repeated again before the integrity test. This would mean a considerable additional time.

The control and control system 78 enables automatic and reliable closing of the inlet control valve 66 (as well as the other control valves 70 . 74 ) with an electric or pneumatic drive, which closes a closing body via a predefined path and under a defined and controlled force. The risk of incomplete or too weak closing of the inlet control valve 66 by the operator is excluded.

To step 5 : The risks of filling the disposable filtration device 10 with product and the complete venting correspond to those already related to step 1 have been described. With regard to the avoidance or minimization of these risks, reference is therefore made to the statements made there.

To step 6 : The filtration of the product under permanent monitoring and, if necessary, control of the inlet pressure or outlet pressure should generally be carried out under constant flow conditions.

Usually has a disposable filtration device 10 depending on filter surface and product a limited capacity. This means that after a certain amount of filtration, the pores of the filter begin to clog gradually, resulting in a rise in the inlet pressure at constant flow. This is due to the pressure limit of the disposable filtration device 10 however, limited and must not be exceeded to rupture the disposable filtration device 10 or to avoid leakage. In the manual process, therefore, the pressure must be constantly monitored and controlled by the operator.

The automated disposable filtration device 10 connected to the inlet pressure sensor 64 at the unfiltrate entrance 56 equipped with the help of the control and control system 78 to ensure pressure monitoring continuously and completely. If the case of a pressure increase, can by throttling or switching off the feed pump 80 and / or by closing the Input control valve 66 a critical overpressure situation can be avoided.

To step 7 : The filtration of the product with intermediate post-deaeration if required is also prone to error if manually carried out. On the one hand, it is important to adhere to the correct filtration pressure, on the other hand, certain flow velocities must not be exceeded, for. B. to protect the product from excessive shear forces or to avoid premature blocking. Furthermore, there is the risk in the post-venting that the sterile air filter 54 wetted by incorrect handling and thus impaired in its function.

With the help of the control and control system 78 , the information from the flow sensor 62 at the unfiltrate entrance 56 the disposable filtration device 10 can refer to the speed of the feed pump 80 a desired filtration performance can be adjusted and regulated. This ensures that the specified process parameters are optimally adhered to in order to ensure that the entire filtration process runs as smoothly as possible and gentle on the product.

Another risk in the filtration arises towards the end of the filtration process. The pressure in the system can rise to a critical level if the filters become blocked, which results in the risk of bursting, especially for the hose lines. The risk of bursting can be increased by improper handling.

The control and control system 78 can reliably detect the blocking of the filters by constantly monitoring the pressure and the flow. By appropriate regulation of the speed of the feed pump 80 and the inlet control valve 66 The system can be switched off if the filters are blocking.

During filtration, when released from the liquid medium or due to process conditions, air or gas may slowly accumulate in the filter unit and become trapped in the filter unit. This can lead to the extent that the liquid level in the filter unit drops and the upper area of the filter elements themselves is no longer effective for filtration. As a result, the filtration-effective area and thus the filter capacity can be reduced, which represents an economic risk. The control and control system 78 can by constantly monitoring the liquid level with the help of the venting liquid detector 76 automatically initiate intermediate post-deaeration steps to counteract this risk.

When deflating itself there is also the risk that medium in the vent hose line 52 to the sterile air filter 54 can penetrate and then the sterile air filter 54 wetted. Thereafter, a venting of the system is only limited, possibly no longer possible.

By using the vent control valve 74 followed by the venting liquid detector 76 at the outlet of the breather hose line 52 , between the filter capsules 12 and the sterile air filter 54 , can with the help of the control and control system 78 first a controlled and slow venting by opening the venting valve slightly 74 respectively. Once the liquid level reaches the top of the disposable filtration device 10 reached and the liquid in the ascending vent hose line 52 penetrates, detects the venting liquid detector 76 this, and the control and management system 78 Immediately transmits a signal to the bleed control valve 74 , which is closed immediately, even before the liquid the sterile air filter 54 reached.

To step 8th : When expelling product residual fluid after filtration has finished and rinsing with buffer or water, there is the risk, among other things, that the pressure in the system will rise to a high level after successful expulsion of the product residual fluid, since the wetted filters are not permeable to air.

By the integration of the inlet pressure sensor 64 can the control and control system 78 the performance of the feed pump 80 throttle early and switch off if necessary, if the pressure becomes too high. Furthermore, there is the possibility of the pressure on the vent control valve 74 to regulate. At the same time, via the output liquid detector 68 at the filtrate outlet 58 ensure efficient use of the product residual fluid, as the system detects when all the remaining fluid has been ejected, so no more liquid is ejected.

During subsequent rinsing, the system must be vented again, again there is the risk that the sterile air filter 54 is wetted. Thereafter, a venting of the system is only limited, possibly no longer possible.

By using the vent control valve 74 followed by the venting liquid detector 76 at the outlet of the breather hose line 52 , between the filter capsules 12 and the sterile air filter 54 , can with the help of the control and control system 78 first a controlled and slow venting by opening the venting valve slightly 74 respectively. As soon as the liquid level reaches the top of the disposable filtration device 10 reached and the liquid in the ascending vent hose line 52 penetrates, detects the venting liquid detector 76 this, and the control and management system 78 Immediately transmits a signal to the bleed control valve 74 , which is closed immediately, even before the liquid the sterile air filter 54 reached.

To step 9 : When draining and aerating the disposable filtration device 10 by static idling or active by blanking with air, there is a risk that the system can not safely idle statically when the bleed control valve 74 and / or the input control valve 66 are not open. Basically, it is difficult to determine the current level of depletion of the system, as it is not easily visible to the operator, how much residual fluid is still in the system.

For automatic control of this process step, the bleed control valve 74 and / or the input control valve 66 and the output liquid detector 68 at the filtrate outlet 58 the disposable filtration device 10 included. The bleed control valve 74 and / or the input control valve 66 are automatically opened, and the output liquid detector 68 can safely detect if the disposable filtration device 10 completely emptied statically. In addition, the output liquid detector can 68 detect the successful completion of the emptying process and complete the process step.

When the system is actively depressed with air via the input line, there is a risk that, after the liquid has been successfully ejected, the pressure will increase greatly as the wetted membrane is impermeable to air. To avoid the risk of bursting, is by means of the input pressure sensor 64 at the unfiltrate entrance 56 and the control and management system 78 continuously monitors the pressure. If the case of a pressure increase, can by throttling or switching off the feed pump 80 or by closing the inlet control valve 66 a critical overpressure situation can be avoided.

Of course, further and / or other than the above-explained sensors and control devices for (partially) automated implementation of the above-explained and / or additional or other processes or process steps may be provided.

LIST OF REFERENCE NUMBERS

10

Disposable filtration device

12

filter capsule

14

holder

16

support column

18

crossmember

20

stand

22

holding means

24

pipeline

26

diversion

28

intake valve

30

branch

32

Tri-Clamp Verbinndung

34

Between the hose piece

36

Input hose

38

first sterile connector

40

outlet valve

42

branch

44

Tri-Clamp Verbinndung

46

Between the hose piece

48

Output hose

50

second sterile connector

52

Vent hose

54

Sterile Air Filter

56

Unfiltrateingang

58

filtrate outlet

60

bleed outlet

62

Flow Sensor

64

Inlet pressure sensor

66

Input control valve

68

Starting fluid detector

70

Output control valve

72

Output pressure sensor

74

Vent control valve

76

Venting liquid detector

78

Control and control system

80

feed pump

QUOTES INCLUDE IN THE DESCRIPTION

This list of the documents listed by the applicant has been generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Cited patent literature

• WO 2017/032560 A1 [0003, 0026]

Claims (22)

Automated disposable filtration apparatus (10), in particular for large-volume filtration processes, having an unfiltrate input (56), one or more filter elements, a filtrate output (58) and sensors for detecting specific process parameters and control devices for setting specific process parameters, the sensors and control devices having a external control and control system (78) are arranged, which is set up for the evaluation and processing of sensor data and for controlling the control devices based on one or more control algorithms. Disposable filtration device (10) according to Claim 1 , characterized in that the sensors comprise a at the unfiltrateingang (56) arranged flow sensor (62). Disposable filtration device (10) according to Claim 1 or 2 , characterized in that the sensors comprise an inlet pressure sensor (64) arranged at the unfiltrate inlet (56). Disposable filtration device (10) according to one of the preceding claims, characterized in that the control devices comprise an inlet control valve (66) arranged at the unfiltrate inlet (56). Disposable filtration device (10) according to one of the preceding claims, characterized in that the sensors comprise an output liquid detector (68) arranged at the filtrate outlet (58). Disposable filtration device (10) according to one of the preceding claims, characterized in that the control devices comprise an outlet control valve (70) arranged at the filtrate outlet (58). Disposable filtration device (10) according to one of the preceding claims, characterized in that the sensors comprise an output pressure sensor (72) arranged at the filtrate outlet (58). A disposable filtration device (10) according to any one of the preceding claims, characterized by a sterile air filter (54) connected to a vent outlet (60) of the disposable filtration device (10). Disposable filtration device (10) according to Claim 8 , characterized in that the control means comprise a bleed control valve (74) interposed between the bleed outlet (60) and the sterile air filter (54). Disposable filtration device (10) according to Claim 8 or 9 characterized in that the sensors comprise a venting liquid detector (76) interposed between the venting outlet (60) and the sterile air filter (54). Disposable filtration device (10) according to one of the preceding claims, characterized in that the control devices comprise an input-side feed pump (80) whose delivery rate is adjustable, preferably adjustable. A method of controlling an automated disposable filtration device according to any one of the preceding claims, wherein the control and control system (78) performs at least partially automatically one of the following process steps, preferably successively: - filling the disposable filtration device (10) with a wetting medium and complete venting via the sterile air filter (54); - rinsing and wetting the disposable filtration device (10) or the filter element; - Draining and aerating the disposable filtration device (10) by static idling or active by blanking with the aid of a gaseous medium; - Pre-use filter integrity test with a gaseous medium; - filling the disposable filtration device (10) with a liquid product and complete deaeration; - Filtration of a liquid product with continuous monitoring of the inlet pressure and, preferably, the flow rate; - Filtration of a liquid product with intermediate post-venting of the disposable filtration device (10) as needed; - expelling product residual fluid after completion of the filtration and rinsing with buffer or water or other liquid medium; - Draining and aerating the disposable filtration device (10) by static idling or active by blanking with the aid of a gaseous medium; and - Post-use filter integrity test with a gaseous medium. Method according to Claim 12 characterized in that the filling of the disposable filtration device (10) with wetting medium and / or product is carried out with continuous monitoring of the pressure at the inlet pressure sensor (64) through which the control and control system (78) and the control and control system (78) the power of the feed pump (80) is regulated so that a predetermined maximum pressure is not exceeded. Method according to Claim 12 or 13 characterized in that upon venting and / or deflating the disposable filtration device (10) via the sterile air filter (54), the vent control valve (74) is opened by the control and control system (78) until the venting liquid detector (76) detects liquid, and the control and control system (78) then immediately closes the bleed control valve (74). Method according to one of Claims 12 to 14 characterized in that, when flushing and wetting the disposable filtration device (10) or the filter element, the control and control system (78) obtains information from the flow sensor (62) at the non-filtrate inlet (56) and based thereon regulates the power delivery pump (80), wherein the control and control system (78) preferably simultaneously monitors the pressure at the inlet pressure sensor (64) and adjusts and regulates a desired flushing capacity and desired pressure ratios via the inlet control valve (66) and / or the outlet control valve (70). Method according to one of Claims 12 to 15 characterized in that, when flushing and wetting the disposable filtration device (10) or the filter element, the control and control system (78) alternately controls and / or cycles the vent control valve (74) and the output control valve (70) to provide controlled mixing and / or displacement of a liquid by another liquid. Method according to one of Claims 12 to 16 characterized in that when emptying and venting the disposable filtration device (10) by static idling or actively by blanking with the aid of air, the control and control system (78) opens the vent control valve (74) and / or the output control valve (70). Method according to one of Claims 12 to 17 , Characterized in that, during emptying and venting of the disposable filtration device (10) by static idling Let or actively by blank pressing with the aid of air, the monitoring and control system (78) based on information from the source liquid detector (68) signals that the emptying process is complete , Method according to one of Claims 12 to 18 , characterized in that in the pre-use filter integrity test with a gaseous medium, the control and control system (78) drives an external integrity tester which performs the integrity test itself, the control and control system (78) having a closing body (drive ) controls the control valves so that while the input control valve (66) is closed and the output control valve (70) and the vent control valve (74) are opened. Method according to one of Claims 12 to 19 , characterized in that in the filtration of a product and / or pushing out of product residual liquid after completion of the filtration and rinsing with buffer or water and / or emptying and aerating the disposable filtration device (10), the control and control system (78) Pressure at the inlet pressure sensor (64) continuously monitors and / or obtains information from the flow sensor (62) at the unfiltrate inlet (56), and the control and control system (78) based thereon regulates the feed pump (80) to achieve a particular filtration efficiency and / or that a predetermined pressure is not exceeded. Method according to Claim 20 , characterized in that the control and control system (78) throttles or shuts off the feed pump (80) and / or closes the inlet control valve (66) in the event of excessive pressure increase. Method according to one of Claims 12 to 21 characterized in that upon expulsion of product residual fluid upon completion of the filtration, the control and control system (78) signals based on information from the source fluid detector (68) that the shedding process is completed.

Images